Azelaic acid is a saturated aliphatic dicarboxylic acid having the formula: HOOC—(CH2)7—COOH. It is also known as 1,9-nonanedioic acid.
Azelaic acid is used as a starting material for producing industrial products including polyesters, plasticizers and lubricants. Azelaic acid is also a component of hair- and skin-care products. See, R. H. Liu et al. “Azelaic acid in the treatment of papulopustular rosacea—A systematic review of randomized controlled trials,” Arch. Dermatol., (2006) 142 (8): 1047-1052. For example, Finacea® (azelaic acid) Gel, 15% (Bayer HealthCare Pharmaceuticals Inc. Whippany, N.J.) is prescribed for topical treatment of mild to moderate rosacea.
Large scale synthesis of azelaic acid remains challenging.
Industrially, azelaic acid is produced via ozonolysis of oleic acid followed by dioxygen oxidation, as described by B. Cornils et al. in “Dicarboxylic Acids, Aliphatic: Ullmann's Encyclopedia of Industrial Chemistry,” Wiley (2010); and by E. F. Moran Jr. in “Process for making a C6 to C12 dibasic acid or azelaic acid using ozone generated from carbon dioxide,” US 2003/0010622.
Other azelaic acid syntheses include those described in E. Antonelli et al., “Efficient Oxidative Cleavage of Olefins to Carboxylic Acids with Hydrogen Peroxide Catalyzed by Methyltrioctylammonium Tetrakis(oxodiperoxotungsto) phosphate (3-) under Two-Phase Conditions. Synthetic Aspects and Investigation of the Reaction Course” J. Org. Chem. 1998, 63, 7190-7206; Lemaire et al. in “Method for Preparing Carboxylic Acids by Oxidative Cleavage of a Vicinal Diol” US 2013/0131379; P. L. Alsters, “Process for the Preparation of (Azelaic) Acid from 9-Octadecenedioic Acid,” US 2015/0183704; and S. Dantale et al. “Processes for Making Azelaic Acid and Derivatives Thereof” US 2016/0145182. These references and all publications cited herein are incorporated by reference in their entirety.
There is a need for new synthetic processes for preparing azelaic acid. Particularly, there is a need for viable, cost-effective, efficient scale-up procedures for manufacturing high purity azelaic acid under cGMP conditions for use as an active pharmaceutical ingredient.